PARIS – A panel of blood-based biomarkers for neocortical amyloid burden – a known predictor of progression to Alzheimer’s disease – shows promise as an effective and economical screening test for early identification of individuals at risk for the disease, according to findings from an Australian study highlighted at an international conference on Alzheimer’s disease.
Currently, neocortical amyloid burden is assessable only by expensive positron emission tomography, which requires radiotracers such as Pittsburgh Compound B (PiB) that are not widely available, or by invasive cerebrospinal fluid evaluation, Samantha Burnham, Ph.D., reported at an international conference on Alzheimer’s disease.
After analyzing 273 samples from patients with baseline blood and PiB-PET measurements from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study, the researchers developed a model using 9 blood-based markers (including A beta 1-42, ApoE, and cortisol) to estimate the amount of deposited amyloid in the brain.
That panel of markers had 83% sensitivity and 85% specificity for identifying the level of amyloid deemed to indicate risk of Alzheimer’s, said Dr. Burnham of the Commonwealth Scientific and Industrial Research Organization (CSIRO), Perth, Australia.
Predictions using the panel were also made in 817 nonimaged AIBL study participants. When those participants were grouped according to clinical diagnosis, the percentages of high neocortical amyloid burden were consistent with prior findings in the literature, with 34% of healthy controls, 87% of mild cognitively impaired individuals, and 100% of Alzheimer’s disease patients having a high burden, Dr. Burnham said.
In addition, the panel of markers was assessed in 74 subjects from the Alzheimer’s Disease Neuroimaging Initiative for validation. In that validation study, measurements for two of the markers from the panel were unavailable, and the sensitivity and specificity were slightly lower, at 76%.
Furthermore, when the samples from the AIBL study were reassessed without the two missing markers, the sensitivity and specificity dropped to a level comparable to that seen in the validation study (74%), suggesting that the accuracy in the validation study might have been even greater if all nine markers were available, she noted.
Because neocortical amyloid burden predicts progression to Alzheimer’s disease, and given that the model used in the study accurately predicts neocortical amyloid burden, Dr. Burnham said, it appears likely that the findings will lead to development of a useful, affordable screening test for the early identification of individuals at risk for developing Alzheimer’s disease.
While it is impossible to provide a timeline for development of such a test, as further validation is needed, she added, these findings are indeed a "first stepping stone toward early diagnosis.
"This is a good start toward having a blood-based diagnosis," Dr. Burnham said.
The conference was sponsored by the Alzheimer’s Association. Dr. Burnham had no disclosures relevant to her presentation.